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|
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data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36370634%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36370634%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="1pl41kx6aGFFsq5GvWXod3gsyv7BSyR4ic59Ea0sKhs9mRbw8fAqHbM66zPNL9po">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="1pl41kx6aGFFsq5GvWXod3gsyv7BSyR4ic59Ea0sKhs9mRbw8fAqHbM66zPNL9po">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="1pl41kx6aGFFsq5GvWXod3gsyv7BSyR4ic59Ea0sKhs9mRbw8fAqHbM66zPNL9po">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 36370634 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 36370634"/>
|
||
<input type="hidden" name="email-subject-hash" value="52641614b2e0695481e03591fe9c7c64fbb1180283e460c972a0cd9b74e9473f"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="1pl41kx6aGFFsq5GvWXod3gsyv7BSyR4ic59Ea0sKhs9mRbw8fAqHbM66zPNL9po">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="1pl41kx6aGFFsq5GvWXod3gsyv7BSyR4ic59Ea0sKhs9mRbw8fAqHbM66zPNL9po">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="1pl41kx6aGFFsq5GvWXod3gsyv7BSyR4ic59Ea0sKhs9mRbw8fAqHbM66zPNL9po">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="1pl41kx6aGFFsq5GvWXod3gsyv7BSyR4ic59Ea0sKhs9mRbw8fAqHbM66zPNL9po">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="1pl41kx6aGFFsq5GvWXod3gsyv7BSyR4ic59Ea0sKhs9mRbw8fAqHbM66zPNL9po">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="36370634">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://linkinghub.elsevier.com/retrieve/pii/S2352-3964(22)00503-5"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=36370634&db=pubmed&nlmid=101647039"
|
||
title="See full text options at Elsevier Science"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Elsevier Science"
|
||
data-ga-label="36370634"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-elsevieroa.png" alt="Elsevier Science full text link"><span class="text">
|
||
|
||
Elsevier Science
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/36370634/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=36370634&db=pubmed&nlmid=101647039"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="36370634"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/36370634/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/36370634/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="36370634" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F36370634%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="1pl41kx6aGFFsq5GvWXod3gsyv7BSyR4ic59Ea0sKhs9mRbw8fAqHbM66zPNL9po"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region"><button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title">
|
||
Display options
|
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Association between B-cell depletion and attack risk in neuromyelitis optica spectrum disorder: An exploratory analysis from N-MOmentum, a double-blind, randomised, placebo-controlled, multicentre phase 2/3 trial
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Association between B-cell depletion and attack risk in neuromyelitis optica spectrum disorder: An exploratory analysis from N-MOmentum, a double-blind, randomised, placebo-controlled, multicentre phase 2/3 trial
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||
|
||
</div>
|
||
|
||
|
||
|
||
<span class="citation-doi">
|
||
doi: 10.1016/j.ebiom.2022.104321.
|
||
</span>
|
||
|
||
|
||
|
||
<span class="secondary-date">
|
||
Epub 2022 Nov 10.
|
||
</span>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<div class="expanded-authors" id="short-view-expanded-authors">
|
||
|
||
<div class="authors">
|
||
<h3 class="title">
|
||
Authors
|
||
</h3>
|
||
|
||
|
||
|
||
<div class="authors-list">
|
||
<span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Bennett+JL&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Jeffrey L Bennett">Jeffrey L Bennett</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="University of Colorado School of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA. Electronic address: jeffrey.bennett@cuanschutz.edu." href="#short-view-affiliation-1" ref="linksrc=author_aff">
|
||
1
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Aktas+O&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Orhan Aktas">Orhan Aktas</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany." href="#short-view-affiliation-2" ref="linksrc=author_aff">
|
||
2
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Rees+WA&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="William A Rees">William A Rees</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Horizon Therapeutics plc, Gaithersburg, MD, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
|
||
3
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Smith+MA&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Michael A Smith">Michael A Smith</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Horizon Therapeutics plc, Gaithersburg, MD, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
|
||
3
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Gunsior+M&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Michele Gunsior">Michele Gunsior</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Horizon Therapeutics plc, Gaithersburg, MD, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
|
||
3
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Yan+L&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Li Yan">Li Yan</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Horizon Therapeutics plc, Gaithersburg, MD, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
|
||
3
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=She+D&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Dewei She">Dewei She</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Horizon Therapeutics plc, Gaithersburg, MD, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
|
||
3
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Cimbora+D&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Daniel Cimbora">Daniel Cimbora</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Horizon Therapeutics plc, Gaithersburg, MD, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
|
||
3
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Pittock+SJ&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Sean J Pittock">Sean J Pittock</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Mayo Clinic and Center for MS and Autoimmune Neurology, Rochester, MN, USA." href="#short-view-affiliation-4" ref="linksrc=author_aff">
|
||
4
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Weinshenker+BG&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Brian G Weinshenker">Brian G Weinshenker</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Mayo Clinic, Rochester, MN, USA." href="#short-view-affiliation-5" ref="linksrc=author_aff">
|
||
5
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Paul+F&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Friedemann Paul">Friedemann Paul</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany." href="#short-view-affiliation-6" ref="linksrc=author_aff">
|
||
6
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Marignier+R&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Romain Marignier">Romain Marignier</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuroinflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France." href="#short-view-affiliation-7" ref="linksrc=author_aff">
|
||
7
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Wingerchuk+D&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Dean Wingerchuk">Dean Wingerchuk</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA." href="#short-view-affiliation-8" ref="linksrc=author_aff">
|
||
8
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Cutter+G&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Gary Cutter">Gary Cutter</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="University of Alabama at Birmingham, Birmingham, AL, USA." href="#short-view-affiliation-9" ref="linksrc=author_aff">
|
||
9
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Green+A&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Ari Green">Ari Green</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="UCSF Weill Institute for Neurosciences, Department of Neurology and Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA." href="#short-view-affiliation-10" ref="linksrc=author_aff">
|
||
10
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Hartung+HP&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Hans-Peter Hartung">Hans-Peter Hartung</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia; Department of Neurology, Medical University Vienna, Vienna, Austria; Department of Neurology, Palacky University in Olomouc, Olomouc, Czech Republic." href="#short-view-affiliation-11" ref="linksrc=author_aff">
|
||
11
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Kim+HJ&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Ho Jin Kim">Ho Jin Kim</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, South Korea." href="#short-view-affiliation-12" ref="linksrc=author_aff">
|
||
12
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Fujihara+K&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Kazuo Fujihara">Kazuo Fujihara</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Multiple Sclerosis Therapeutics, Fukushima Medical University and Multiple Sclerosis and Neuromyelitis Optica Center, Southern Tohoku Research Institute for Neuroscience, Koriyama, Japan." href="#short-view-affiliation-13" ref="linksrc=author_aff">
|
||
13
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Levy+M&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Michael Levy">Michael Levy</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA." href="#short-view-affiliation-14" ref="linksrc=author_aff">
|
||
14
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Katz+E&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Eliezer Katz">Eliezer Katz</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Horizon Therapeutics plc, Gaithersburg, MD, USA." href="#short-view-affiliation-3" ref="linksrc=author_aff">
|
||
3
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=Cree+BAC&cauthor_id=36370634"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="Bruce A C Cree">Bruce A C Cree</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA." href="#short-view-affiliation-15" ref="linksrc=author_aff">
|
||
15
|
||
</a></sup><span class="semicolon">; </span></span><span class="authors-list-item "><a class="full-name"
|
||
href="/?term=N-MOmentum+study+investigators%5BCorporate+Author%5D"
|
||
ref="linksrc=author_name_link"
|
||
data-ga-category="search"
|
||
data-ga-action="author_link"
|
||
data-ga-label="N-MOmentum study investigators">N-MOmentum study investigators</a></span>
|
||
</div>
|
||
|
||
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<div class="affiliations">
|
||
<h3 class="title">
|
||
Affiliations
|
||
</h3>
|
||
<ul class="item-list">
|
||
|
||
<li data-affiliation-id="short-view-affiliation-1"
|
||
id="short-view-affiliation-1"
|
||
><sup class="key">1</sup> University of Colorado School of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO, USA. Electronic address: jeffrey.bennett@cuanschutz.edu.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-2"
|
||
id="short-view-affiliation-2"
|
||
><sup class="key">2</sup> Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-3"
|
||
id="short-view-affiliation-3"
|
||
><sup class="key">3</sup> Horizon Therapeutics plc, Gaithersburg, MD, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-4"
|
||
id="short-view-affiliation-4"
|
||
><sup class="key">4</sup> Mayo Clinic and Center for MS and Autoimmune Neurology, Rochester, MN, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-5"
|
||
id="short-view-affiliation-5"
|
||
><sup class="key">5</sup> Mayo Clinic, Rochester, MN, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-6"
|
||
id="short-view-affiliation-6"
|
||
><sup class="key">6</sup> Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-7"
|
||
id="short-view-affiliation-7"
|
||
><sup class="key">7</sup> Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuroinflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-8"
|
||
id="short-view-affiliation-8"
|
||
><sup class="key">8</sup> Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-9"
|
||
id="short-view-affiliation-9"
|
||
><sup class="key">9</sup> University of Alabama at Birmingham, Birmingham, AL, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-10"
|
||
id="short-view-affiliation-10"
|
||
><sup class="key">10</sup> UCSF Weill Institute for Neurosciences, Department of Neurology and Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-11"
|
||
id="short-view-affiliation-11"
|
||
><sup class="key">11</sup> Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia; Department of Neurology, Medical University Vienna, Vienna, Austria; Department of Neurology, Palacky University in Olomouc, Olomouc, Czech Republic.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-12"
|
||
id="short-view-affiliation-12"
|
||
><sup class="key">12</sup> Department of Neurology, Research Institute and Hospital of National Cancer Center, Goyang, South Korea.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-13"
|
||
id="short-view-affiliation-13"
|
||
><sup class="key">13</sup> Department of Multiple Sclerosis Therapeutics, Fukushima Medical University and Multiple Sclerosis and Neuromyelitis Optica Center, Southern Tohoku Research Institute for Neuroscience, Koriyama, Japan.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-14"
|
||
id="short-view-affiliation-14"
|
||
><sup class="key">14</sup> Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.</li>
|
||
|
||
<li data-affiliation-id="short-view-affiliation-15"
|
||
id="short-view-affiliation-15"
|
||
><sup class="key">15</sup> UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA.</li>
|
||
|
||
</ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<ul class="identifiers" id="short-view-identifiers">
|
||
|
||
<li>
|
||
<span class="identifier pubmed">
|
||
<span class="id-label">
|
||
|
||
PMID:
|
||
|
||
</span>
|
||
|
||
|
||
<strong class="current-id" title="PubMed ID">36370634</strong>
|
||
|
||
|
||
|
||
</span>
|
||
|
||
</li>
|
||
|
||
<li>
|
||
<span class="identifier pmc">
|
||
<span class="id-label">
|
||
|
||
PMCID:
|
||
|
||
</span>
|
||
|
||
|
||
<a class="id-link"
|
||
target="_blank"
|
||
rel="noopener"
|
||
ref="linksrc=article_id_link&article_id=PMC9664402&id_type=PMC"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/PMC9664402/"
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMCID"
|
||
>
|
||
PMC9664402
|
||
</a>
|
||
|
||
|
||
|
||
</span>
|
||
|
||
</li>
|
||
|
||
<li>
|
||
<span class="identifier doi">
|
||
<span class="id-label">
|
||
|
||
DOI:
|
||
|
||
</span>
|
||
|
||
|
||
<a class="id-link"
|
||
target="_blank"
|
||
rel="noopener"
|
||
ref="linksrc=article_id_link&article_id=10.1016/j.ebiom.2022.104321&id_type=DOI"
|
||
href="https://doi.org/10.1016/j.ebiom.2022.104321"
|
||
data-ga-category="full_text"
|
||
data-ga-action="DOI"
|
||
>
|
||
10.1016/j.ebiom.2022.104321
|
||
</a>
|
||
|
||
|
||
|
||
</span>
|
||
|
||
</li>
|
||
|
||
</ul>
|
||
|
||
|
||
|
||
<div class="in-clipboard-label " hidden>
|
||
Item in Clipboard
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</header>
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<strong class="sub-title">
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Background:
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Inebilizumab is an anti-CD19 antibody approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults with aquaporin-4 autoantibodies. The relationship between B-cell, plasma-cell (PC), and immunoglobulin depletion with longitudinal reductions in NMOSD activity after inebilizumab treatment was characterised post hoc in an exploratory analysis from the N-MOmentum study (<a href="http://clinicaltrials.gov/show/NCT02200770" title="See in ClinicalTrials.gov">NCT02200770</a>).
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<strong class="sub-title">
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Methods:
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</strong>
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Peripheral blood CD20+ B cells, PC gene signature, and immunoglobulin levels were assessed throughout N-MOmentum (follow-up ≥2.5 years); correlations with clinical metrics and magnetic resonance imaging (MRI) lesion activity were assessed.
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Findings:
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Inebilizumab induced durable B-cell and PC depletion within 1 week versus placebo. Although no association was observed between B-cell counts at time of attack and NMOSD activity, depth of B-cell depletion after the first dosing period correlated with clinical outcomes. All participants receiving inebilizumab demonstrated a robust long-term therapeutic response, and participants with ≤4 cells/μL after the first 6-month dosing interval had persistently deeper B-cell depletion, lower annualised attack rates (estimated rate [95% CI]: 0.034 [0.024-0.04] vs 0.086 [0.056-0.12]; p = 0.045), fewer new/enlarging T2 MRI lesions (0.49 [0.43-0.56] vs 1.36 [1.12-1.61]; p < 0.0001), and a trend towards decreased Expanded Disability Status Scale worsening (0.076 [0.06-0.10] vs 0.14 [0.10-0.18]; p = 0.093). Antibodies to inebilizumab, although present in a proportion of treated participants, did not alter outcomes.
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Interpretation:
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</strong>
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This analysis suggests that compared with placebo, inebilizumab can provide specific, rapid, and durable depletion of B cells in participants with NMOSD. Although deep and persistent CD20+ B-cell depletion correlates with long-term clinical stability, early, deep B-cell depletion correlates with improved disease activity metrics in the first 2 years.
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<p>
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<strong class="sub-title">
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Funding:
|
||
</strong>
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Horizon Therapeutics (formerly from Viela Bio/MedImmune).
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<p>
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<strong class="sub-title">
|
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Keywords:
|
||
</strong>
|
||
|
||
Anti-CD19 monoclonal antibody; Aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder; B-cell suppression; Devic disease.
|
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</p>
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<p class="copyright" id="copyright">
|
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Copyright © 2022 Horizon Therapeutics plc. Published by Elsevier B.V. All rights reserved.
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|
||
<a href="/disclaimer/" target="_blank" data-ga-category="literature_resources"
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data-ga-action="disclaimer_link" data-ga-label="under_abstract">PubMed Disclaimer</a>
|
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<div class="conflict-of-interest" id="conflict-of-interest">
|
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<h2 class="title">
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||
Conflict of interest statement
|
||
</h2>
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<div class="statement">
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">Declaration of interests J.L.Bennett reports payment for study design/consultation from MedImmune; personal fees from AbbVie, Alexion, Antigenomycs, BeiGene, Chugai, Clene Nanomedicine, Genentech, Genzyme, Reistone Bio, Roche, and TG; grants from Alexion, the National Institutes of Health, and Novartis. In addition, Dr Bennett has a patent ‘Compositions and methods for the treatment of neuromyelitis optica’. O.Aktas reports grants from the German Research Foundation (DFG) and the German Ministry of Education and Research (BMBF); grants and personal fees from Bayer HealthCare, Biogen, Genzyme, Horizon Therapeutics (formerly from Viela Bio), Novartis, and Teva; and personal fees from Almirall, MedImmune, Merck Serono, and Roche. W.A.Rees, M.A.Smith, D.She, and D.Cimbora are employees of Horizon Therapeutics (formerly Viela Bio) and own stock. L.Yan, M.Gunsior, and E.Katz are former employees of Horizon Therapeutics. S.J.Pittock reports grants, personal fees, and non-financial support from Alexion Pharmaceuticals, Inc.; grants from Autoimmune Encephalitis Alliance and Grifols; grants, personal fees, non-financial support, and other from Horizon Therapeutics (formerly from Viela Bio) and MedImmune; personal fees for consulting services from Astellas; grants, personal fees, non-financial support and other from Roche/Genentech; personal fees for consulting services from UCB; and has a patent #9,891,219 (Application#12-573942) ’Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody Positive’. B.G.Weinshenker received payments for serving as chair of attack adjudication committees for clinical trials in NMOSD for Alexion, MedImmune, and Viela Bio/Horizon Therapeutics; has consulted with Chugai, Genentech, Horizon Therapeutics, Mitsubishi Tanabe Pharma, and Roche Pharmaceuticals; and has a patent for NMO-IgG for diagnosis of neuromyelitis optica, with royalties paid by Hospices Civils de Lyon, MVZ Labor PD Dr. Volkmann und Kollegen GbR, University of Oxford, and RSR. F.Paul has received research support, speaker honoraria, and travel reimbursement from Bayer, Biogen Idec, Merck Serono, Novartis, Sanofi Genzyme, and Teva; is supported by the German Research Council (DFG Exc 257) and the German Competence Network for Multiple Sclerosis; has received travel reimbursement from the Guthy-Jackson Charitable Foundation; and serves on the steering committee of the OCTIMS study, sponsored by Novartis. R.Marignier reports personal fees for consulting from Alexion, Horizon Therapeutics (formerly Viela Bio), Roche, and UCB. D.Wingerchuk reports personal fees from Biogen, Celgene, Genentech, MedImmune, Mitsubishi Tanabe, Novartis, Reistone Biopharma, and TG Therapeutics; research support paid to the Mayo Clinic by Alexion and Terumo BCT; and has served on a clinical trial adjudication committee for Horizon Therapeutics (formerly Viela Bio) and MedImmune. G.Cutter has received personal fees for participation on Data and Safety Monitoring Boards from AstraZeneca, Avexis Pharmaceuticals, BioLineRx, Brainstorm Cell Therapeutics, Bristol Myers Squibb/Celgene, CSL Behring, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (Obesity Policy Research Unit oversight committee), Galmed Pharmaceuticals, Hisun Pharmaceutical, Horizon Pharmaceuticals (formerly Viela Bio), Mapi Pharma, Merck, Merck/Pfizer, the National Heart, Lung, and Blood Institute (Protocol Review Committee), Neurim Pharmaceuticals, Novartis, OncoImmune, OPKO Biologics, Orphazyme, Reata Pharmaceuticals, Sanofi-Aventis, Teva Pharmaceuticals, and Vivus; personal fees for consulting or advisory board participation from BioDelivery Sciences International, Biogen, Click Therapeutics, Genentech, Genzyme, GW Pharmaceuticals, Immunic, Klein Buendel, MedDay, MedImmune, NeuroGenesis, Novartis, Osmotica Pharmaceuticals, Perception Neurosciences, Recursion/Cerexis Pharmaceuticals, Roche, and TG Therapeutics; is employed by the University of Alabama at Birmingham, AL, USA; and is President of Pythagoras, Inc., a private consulting company based in Birmingham, AL, USA. A.Green reports grants from the Conrad N. Hilton Foundation and the Tom Sherak MS Hope Foundation; other financial relationships (for activities as expert witness, associate editor, advisory board/steering committee participation, and endpoint adjudication) with Bionure, Inception Sciences, JAMA Neurology, MedImmune/Horizon Therapeutics (formerly Viela Bio), Mylan, Synthon, and Trims Pharma; and personal fees from and other financial relationships with Pipeline Therapeutics. H.-P.Hartung has received fees for consulting, speaking, and serving on steering committees from Bayer HealthCare, Biogen Idec, Celgene Receptos, CSL Behring, GeNeuro, Genzyme, Horizon Therapeutics (formerly Viela Bio), MedDay, MedImmune, Merck Serono, Novartis, Roche, Sanofi, and TG Therapeutics with approval by the Rector of Heinrich Heine University Düsseldorf. H.J.Kim has received a grant from the National Research Foundation of Korea; consultancy/speaker fees or research support from Alexion, AprilBio, Celltrion, Daewoong Pharmaceutical, Eisai, GC Pharma, HanAll Biopharma, Horizon Therapeutics (formerly Viela Bio), Kolon Life Science, MedImmune, Merck Serono, Mitsubishi Tanabe Pharma, Novartis, Sanofi Genzyme, Teva-Handok, and UCB; and is a co-editor for the Multiple Sclerosis Journal and an associate editor for the Journal of Clinical Neurology. K.Fujihara has received fees for consulting, speaking, and serving on steering committees from AbbVie, Alexion, Asahi Kasei Kuraray Medical Co., Biogen, Chugai/Roche, Eisai, Japan Tobacco, MedImmune/Viela Bio, Merck, Merck Biopharma, Mitsubishi Tanabe Pharma, Novartis, Teijin, Takeda Pharmaceutical Company, and UCB; and a grant-in-aid for scientific research from the Ministry of Health, Labour and Welfare of Japan. M.Levy currently receives research support from Acorda Therapeutics, Alexion, Alnylam Pharmaceuticals, ApoPharma, Maryland Technology Development Corporation, the National Institutes of Health, Sanofi Genzyme, and Shire/Takeda; has received personal compensation for consultation with Acorda Therapeutics, Alexion, and Genzyme; and serves on the scientific advisory boards for Acorda Therapeutics, Alexion, and Quest Diagnostics. B.A.C.Cree reports personal compensation for consulting from Alexion, Atara Biotherapeutics, Autobahn Therapeutics, Avotres Inc., Biogen, Boston Pharma, EMD Serono, Gossamer Bio, Hexal/Sandoz, Horizon Therapeutics, Neuron23, Novartis, Sanofi, Siemens, TG Therapeutics, and Therini Bio; and has received research support from Genentech.</p>
|
||
|
||
|
||
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|
||
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|
||
|
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|
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||
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||
<strong class="figure-label">
|
||
<p> Fig. 1 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Participant flow in N-MOmentum. </b> For…</div>
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<p> Fig. 1 </p>
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||
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<div class="figure-caption-contents"><b> Participant flow in N-MOmentum. </b> For analysis purposes, participants were divided into three groups:…</div>
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Fig. 1
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Participant flow in N-MOmentum.</b> For analysis purposes, participants were divided into three groups: “RCP inebilizumab” (participants randomised to inebilizumab during the RCP), “RCP placebo” (participants randomised to placebo during the RCP), and “any inebilizumab” (participants who received inebilizumab at any point during the study, including those from the RCP inebilizumab group and all participants in the OLP; shaded in pink). OLP = open-label period, RCP = randomised controlled period.</div>
|
||
|
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<div class="figure-caption-contents"><b> Kinetics of B-cell and immunoglobulin… </b></div>
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<p> Fig. 2 </p>
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<div class="figure-caption-contents"><b> Kinetics of B-cell and immunoglobulin depletion during the study. (a) </b> Total CD20+ B-cell…</div>
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Fig. 2
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||
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|
||
<div class="figure-caption-contents"><b>Kinetics of B-cell and immunoglobulin depletion during the study. (a)</b> Total CD20+ B-cell counts. <b>(b)</b> Plasma-cell gene signature normalised to a pool of 10 HDs using the ddCT method. <b>(c)</b> Total immunoglobulin, <b>(d)</b> immunoglobulin G, <b>(e)</b> immunoglobulin M, <b>(f)</b> immunoglobulin A, and <b>(g)</b> immunoglobulin E concentrations over time during the RCP in placebo-treated (in grey) and inebilizumab-treated (in red) participants. Points show medians and shaded regions show IQRs. Dashed black lines show LLOQ of 0.2 cells/μL for FACS assays. Samples with counts below the LLOQ were imputed to 0.05 cells/μL. Mann–Whitney <i>U</i> test between dose groups; <i>p</i> > 0.05 where <i>p</i> not noted. Vertical dashed lines show when participants were transitioned to the OLP and the placebo cohort was administered two inebilizumab doses; the inebilizumab cohort was given an additional maintenance dose. ddCT = delta delta cycle threshold, FACS = fluorescence-activated cell sorting, FC = fold change, HD = healthy donor, IQR = interquartile range, LLOQ = lower limit of quantification, OLP = open-label period, RCP = randomised controlled period.</div>
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||
|
||
|
||
<div class="figure-caption-contents"><b> Kinetics of B-cell and immunoglobulin depletion during the study. (a) </b> Total CD20+ B-cell…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
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|
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<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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<strong class="figure-label">
|
||
Fig. 2
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Kinetics of B-cell and immunoglobulin depletion during the study. (a)</b> Total CD20+ B-cell counts. <b>(b)</b> Plasma-cell gene signature normalised to a pool of 10 HDs using the ddCT method. <b>(c)</b> Total immunoglobulin, <b>(d)</b> immunoglobulin G, <b>(e)</b> immunoglobulin M, <b>(f)</b> immunoglobulin A, and <b>(g)</b> immunoglobulin E concentrations over time during the RCP in placebo-treated (in grey) and inebilizumab-treated (in red) participants. Points show medians and shaded regions show IQRs. Dashed black lines show LLOQ of 0.2 cells/μL for FACS assays. Samples with counts below the LLOQ were imputed to 0.05 cells/μL. Mann–Whitney <i>U</i> test between dose groups; <i>p</i> > 0.05 where <i>p</i> not noted. Vertical dashed lines show when participants were transitioned to the OLP and the placebo cohort was administered two inebilizumab doses; the inebilizumab cohort was given an additional maintenance dose. ddCT = delta delta cycle threshold, FACS = fluorescence-activated cell sorting, FC = fold change, HD = healthy donor, IQR = interquartile range, LLOQ = lower limit of quantification, OLP = open-label period, RCP = randomised controlled period.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
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|
||
|
||
</figure>
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||
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<figure class="figure-item "
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itemscope itemtype="http://schema.org/ImageObject"
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data-label-slug="fig-2">
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||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/7fa3c462bab1/gr2g.jpg"
|
||
itemprop="contentUrl"
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||
aria-describedby="figure-caption-3"
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role="button"
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data-image-width="714"
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data-image-height="338"
|
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data-image-alt="Fig. 2"
|
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data-pmc-id="PMC9664402"
|
||
data-figure-id="fig2">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-3"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/da5d9d80b014/gr2ac.gif"
|
||
alt="Fig. 2" />
|
||
</a>
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|
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<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="714">
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<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="338">
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|
||
|
||
|
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|
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|
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|
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<strong class="figure-label">
|
||
<p> Fig. 2 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Kinetics of B-cell and immunoglobulin… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 2 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Kinetics of B-cell and immunoglobulin depletion during the study. (a) </b> Total CD20+ B-cell…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
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|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Fig. 2
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Kinetics of B-cell and immunoglobulin depletion during the study. (a)</b> Total CD20+ B-cell counts. <b>(b)</b> Plasma-cell gene signature normalised to a pool of 10 HDs using the ddCT method. <b>(c)</b> Total immunoglobulin, <b>(d)</b> immunoglobulin G, <b>(e)</b> immunoglobulin M, <b>(f)</b> immunoglobulin A, and <b>(g)</b> immunoglobulin E concentrations over time during the RCP in placebo-treated (in grey) and inebilizumab-treated (in red) participants. Points show medians and shaded regions show IQRs. Dashed black lines show LLOQ of 0.2 cells/μL for FACS assays. Samples with counts below the LLOQ were imputed to 0.05 cells/μL. Mann–Whitney <i>U</i> test between dose groups; <i>p</i> > 0.05 where <i>p</i> not noted. Vertical dashed lines show when participants were transitioned to the OLP and the placebo cohort was administered two inebilizumab doses; the inebilizumab cohort was given an additional maintenance dose. ddCT = delta delta cycle threshold, FACS = fluorescence-activated cell sorting, FC = fold change, HD = healthy donor, IQR = interquartile range, LLOQ = lower limit of quantification, OLP = open-label period, RCP = randomised controlled period.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
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itemprop="associatedMedia"
|
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data-slide-index="4"
|
||
data-label-slug="fig-3">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/ca5eeab45d72/gr3ab.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-4"
|
||
role="button"
|
||
data-image-width="714"
|
||
data-image-height="903"
|
||
data-image-alt="Fig. 3"
|
||
data-pmc-id="PMC9664402"
|
||
data-figure-id="fig3">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-4"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/edb3bf3942fd/gr3ab.gif"
|
||
alt="Fig. 3" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="714">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="903">
|
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|
||
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|
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|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 3 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Decreases in NMOSD progression observed… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 3 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Decreases in NMOSD progression observed with long-term inebilizumab treatment. </b> <b> (a) </b> AAR. <b> (b) </b> Annualised…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Fig. 3
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Decreases in NMOSD progression observed with long-term inebilizumab treatment.</b><b>(a)</b> AAR. <b>(b)</b> Annualised rate of EDSS worsening. <b>(c)</b> Annualised rate of new/enlarging MRI T2 lesions (only participants randomised to inebilizumab are included). <b>(d)</b> Annualised NMOSD-related inpatient hospitalisation rate. Plots show rates in placebo-treated participants during RCP (in grey) and in all participants during the first dosing period of inebilizumab treatment (first dosing interval), and yearly afterwards (in blue). The final bar in each plot displays the combined rate of each endpoint after 2.5 years or more of continued inebilizumab treatment. Mean data with error bars showing 95% CI estimated by negative binomial regression. AAR = annualised attack rate, CI = confidence interval, EDSS = Expanded Disability Status Scale, MRI = magnetic resonance imaging, NMOSD = neuromyelitis optica spectrum disorder, RCP = randomised controlled period.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item "
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
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data-slide-index="5"
|
||
data-label-slug="fig-3">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/b3515f1f56ae/gr3cd.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-5"
|
||
role="button"
|
||
data-image-width="714"
|
||
data-image-height="949"
|
||
data-image-alt="Fig. 3"
|
||
data-pmc-id="PMC9664402"
|
||
data-figure-id="fig3">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-5"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/edb3bf3942fd/gr3ab.gif"
|
||
alt="Fig. 3" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="714">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="949">
|
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|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 3 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Decreases in NMOSD progression observed… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 3 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Decreases in NMOSD progression observed with long-term inebilizumab treatment. </b> <b> (a) </b> AAR. <b> (b) </b> Annualised…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Fig. 3
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Decreases in NMOSD progression observed with long-term inebilizumab treatment.</b><b>(a)</b> AAR. <b>(b)</b> Annualised rate of EDSS worsening. <b>(c)</b> Annualised rate of new/enlarging MRI T2 lesions (only participants randomised to inebilizumab are included). <b>(d)</b> Annualised NMOSD-related inpatient hospitalisation rate. Plots show rates in placebo-treated participants during RCP (in grey) and in all participants during the first dosing period of inebilizumab treatment (first dosing interval), and yearly afterwards (in blue). The final bar in each plot displays the combined rate of each endpoint after 2.5 years or more of continued inebilizumab treatment. Mean data with error bars showing 95% CI estimated by negative binomial regression. AAR = annualised attack rate, CI = confidence interval, EDSS = Expanded Disability Status Scale, MRI = magnetic resonance imaging, NMOSD = neuromyelitis optica spectrum disorder, RCP = randomised controlled period.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
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|
||
data-slide-index="6"
|
||
data-label-slug="fig-4">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/848af5ee95ee/gr4.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-6"
|
||
role="button"
|
||
data-image-width="689"
|
||
data-image-height="610"
|
||
data-image-alt="Fig. 4"
|
||
data-pmc-id="PMC9664402"
|
||
data-figure-id="fig4">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-6"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/81e9f378c1a6/gr4.gif"
|
||
alt="Fig. 4" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="689">
|
||
<meta itemprop="height" itemtype="http://schema.org/ImageObject" content="610">
|
||
|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 4 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Temporal relationship between CD20+ B-cell… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 4 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> Temporal relationship between CD20+ B-cell counts and attacks. </b> Box plot of CD20+ B-cell…</div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Fig. 4
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>Temporal relationship between CD20+ B-cell counts and attacks.</b> Box plot of CD20+ B-cell counts in all samples drawn from participants who never experienced attacks, in samples drawn preceding attacks (sample draws 15–115 days preceding attacks), during attack assessment, and after attacks (sample draws 8–200 days after attack). “Other samples” refers to samples that were drawn from participants who experienced attacks, but not directly preceding the attack, directly after the attack, or during the attack. The bold bar shows the median, the box shows the IQR, and the whiskers show the range of data. IQR = interquartile range, LLOQ = lower limit of quantification, WB = whole blood.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
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|
||
data-slide-index="7"
|
||
data-label-slug="fig-5">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/7d42fc944ab1/gr5.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-7"
|
||
role="button"
|
||
data-image-width="714"
|
||
data-image-height="622"
|
||
data-image-alt="Fig. 5"
|
||
data-pmc-id="PMC9664402"
|
||
data-figure-id="fig5">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-7"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/0f7a672cf5f4/gr5.gif"
|
||
alt="Fig. 5" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="714">
|
||
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|
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|
||
|
||
<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
|
||
|
||
<div class="caption-wrap">
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 5 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> B- </b> <b> cell kinetics in the… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Fig. 5 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b> B- </b> <b> cell kinetics in the first dosing interval of inebilizumab predict long-term deep… </b></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-7" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Fig. 5
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><b>B-</b><b>cell kinetics in the first dosing interval of inebilizumab predict long-term deep B-cell depletion. (a)</b> Profile plot of CD20+ B-cell counts in individual patients throughout the first dosing interval with inebilizumab. <b>(b)</b> Total CD20+ B-cell counts over 3 years of inebilizumab treatment in patients with B-cell counts >4 cells/μL and ≤4 cells/μL at the end of the first dosing period. Points show medians ± IQR. Mann–Whitney <i>U</i> test was used to calculate <i>p</i> values. IQR = interquartile range, LLOQ = lower limit of quantification.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
</figure>
|
||
|
||
<figure class="figure-item tail"
|
||
itemscope itemtype="http://schema.org/ImageObject"
|
||
itemprop="associatedMedia"
|
||
data-slide-index="8"
|
||
data-label-slug="fig-6">
|
||
<a class="figure-link"
|
||
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/1f9af5284770/gr6ab.jpg"
|
||
itemprop="contentUrl"
|
||
aria-describedby="figure-caption-8"
|
||
role="button"
|
||
data-image-width="714"
|
||
data-image-height="700"
|
||
data-image-alt="Fig. 6"
|
||
data-pmc-id="PMC9664402"
|
||
data-figure-id="fig6">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-8"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3a0/9664402/570b1dbd0f38/gr6ab.gif"
|
||
alt="Fig. 6" />
|
||
</a>
|
||
|
||
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="714">
|
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|
||
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|
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|
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<div class="caption-wrap">
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<p> Fig. 6 </p>
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<div class="figure-caption-contents"><b> Improvement occurs in all participant… </b></div>
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<strong class="figure-label">
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<p> Fig. 6 </p>
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<div class="figure-caption-contents"><b> Improvement occurs in all participant subgroups over time. </b> <b> (a) </b> AAR. <b> (b) </b> Annualised rate…</div>
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Fig. 6
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<div class="figure-caption-contents"><b>Improvement occurs in all participant subgroups over time.</b><b>(a)</b> AAR. <b>(b)</b> Annualised rate of EDSS worsening. <b>(c)</b> Annualised rate of new/enlarging T2 MRI lesions (only participants randomised to inebilizumab are included). <b>(d)</b> Annualised inpatient hospitalisation rate split by patients with ≤4 cells/μL or >4 cells/μL after the first inebilizumab dosing interval (6 months after treatment). Plot shows rates in placebo-treated participants during the RCP (in grey), then in both inebilizumab-treated participant groups during the first dosing period of inebilizumab treatment (first dosing interval), and yearly afterwards (in blue and red). The final bars in each plot display the combined rate of each endpoint after 2.5 years or more of continued inebilizumab treatment. Mean data with error bars showing 95% CI estimated by negative binomial regression. AAR = annualised attack rate, CI = confidence interval, EDSS = Expanded Disability Status Scale, MRI = magnetic resonance imaging, RCP = randomised controlled period.</div>
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<p> Fig. 6 </p>
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<div class="figure-caption-contents"><b> Improvement occurs in all participant… </b></div>
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<strong class="figure-label">
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<p> Fig. 6 </p>
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</strong>
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|
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<div class="figure-caption-contents"><b> Improvement occurs in all participant subgroups over time. </b> <b> (a) </b> AAR. <b> (b) </b> Annualised rate…</div>
|
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|
||
|
||
|
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<figcaption id="figure-caption-9" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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Fig. 6
|
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</strong>
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|
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|
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|
||
<div class="figure-caption-contents"><b>Improvement occurs in all participant subgroups over time.</b><b>(a)</b> AAR. <b>(b)</b> Annualised rate of EDSS worsening. <b>(c)</b> Annualised rate of new/enlarging T2 MRI lesions (only participants randomised to inebilizumab are included). <b>(d)</b> Annualised inpatient hospitalisation rate split by patients with ≤4 cells/μL or >4 cells/μL after the first inebilizumab dosing interval (6 months after treatment). Plot shows rates in placebo-treated participants during the RCP (in grey), then in both inebilizumab-treated participant groups during the first dosing period of inebilizumab treatment (first dosing interval), and yearly afterwards (in blue and red). The final bars in each plot display the combined rate of each endpoint after 2.5 years or more of continued inebilizumab treatment. Mean data with error bars showing 95% CI estimated by negative binomial regression. AAR = annualised attack rate, CI = confidence interval, EDSS = Expanded Disability Status Scale, MRI = magnetic resonance imaging, RCP = randomised controlled period.</div>
|
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<span class="docsum-authors full-authors">Bennett JL, Pittock SJ, Paul F, Kim HJ, Irani SR, O'Connor KC, Patterson KR, Smith MA, Gunsior M, Mittereder N, Rees WA, Cimbora D, Cree BAC.</span>
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Wingerchuk D.M., Lennon V.A., Lucchinetti C.F., Pittock S.J., Weinshenker B.G. The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6:805–815.
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aria-label="Dropdown menu for keyword Clinical Trial, Phase II"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Clinical Trial, Phase III
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<div id="mesh-terms" class="mesh-terms keywords-section">
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MeSH terms
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Adult
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Autoantibodies
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Neuromyelitis Optica* / drug therapy
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